Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.
Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.
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DOI：
10.3389/fphar.2021.657724
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ma YP
中科院分区：
文献类型：
--
作者：
Liu HM;Guo CL;Zhang YF;Chen JF;Liang ZP;Yang LH;Ma YP
益母草碱是从益母草中分离得到的一种活性天然生物碱化合物，具有良好的抗实体瘤活性。本研究的目的是探讨益母草碱是否能够抑制慢性粒细胞白血病（CML）恶性肿瘤。本研究发现益母草碱剂量依赖性地抑制CML细胞的增殖、迁移、集落形成和促进细胞凋亡。此外，益母草碱显着降低体内CML异种移植物的生长。在机制上，益母草碱上调SOCS 5表达，从而导致JAK 2/STAT 3信号转导抑制。通过siRNA沉默SOCS 5消除了益母草碱对CML细胞的作用，表明SOCS 5介导了益母草碱的抗白血病作用。值得注意的是，我们观察到miR-18 a-5 p在CML细胞中显著增加。用益母草碱处理CML细胞显著降低miR-18 a-5 p表达。此外，我们发现miR-18 a-5 p通过直接靶向SOCS 5的3′-UTR抑制SOCS 5。益母草碱诱导的miR-18 a-5 p下调通过解除miR-18 a-5 p对SOCS 5表达的抑制而降低CML细胞的生物学活性。综上所述，益母草碱通过调节miR-18 a-5 p/SOCS 5/JAK 2/STAT 3轴在CML中发挥显著的抗白血病功效。
Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth in vivo. Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3′-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.
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影响因子：
5.7
作者：
Stella, Stefania;Tirro, Elena;Vigneri, Paolo
通讯作者：
Vigneri, Paolo
影响因子：
6.2
作者：
Hsu, T-I;Hsu, C-H;Lee, K-H;Lin, J-T;Chen, C-S;Chang, K-C;Su, C-Y J.;Hsiao, M.;Lu, P-J
通讯作者：
Lu, P-J
影响因子：
7.9
作者：
Liu, X. H.;Pan, L. L.;Zhu, Y. Z.
通讯作者：
Zhu, Y. Z.
DOI：
10.1186/bcr3428
发表时间：
2013-05-24
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Godfrey AC;Xu Z;Weinberg CR;Getts RC;Wade PA;DeRoo LA;Sandler DP;Taylor JA
通讯作者：
Taylor JA
影响因子：
2.9
作者：
Fan G;Jiao J;Shen F;Ren Q;Wang Q;Chu F
通讯作者：
Chu F